EDS and Eosinophilic Esophagitis (EoE)

Ehlers-Danlos Syndrome (EDS) and Eosinophilic Esophagitis (EoE) are two complex conditions that, at first glance, appear unrelated—one affects connective tissues, while the other involves inflammation of the esophagus. Yet emerging research has uncovered a significant overlap between these conditions, offering new insights into their shared biology and the importance of integrated care.

What is Eosinophilic Esophagitis (EoE)?

EoE is a chronic immune-mediated condition characterized by inflammation of the esophagus, caused by eosinophils—a type of white blood cell that reacts to allergens or immune triggers. It often presents with symptoms like difficulty swallowing (dysphagia), food impaction, reflux that doesn’t respond to acid-blockers, and, in children, failure to thrive.

The prevalence of EoE has grown rapidly over the last two decades, now affecting approximately 1 in 1,000 individuals. Its rise has been attributed to improved recognition and potentially increasing environmental or dietary triggers. EoE is often associated with other allergic conditions, including asthma, eczema, and food allergies.

What is Ehlers-Danlos Syndrome (EDS)?

EDS is a group of inherited disorders that affect the body’s connective tissues—those that support the skin, joints, blood vessels, and organs. The most common type, hypermobile EDS (hEDS), is characterized by joint hypermobility, stretchy skin, frequent dislocations, and fragile tissues. Gastrointestinal (GI) symptoms are also prevalent in EDS, including constipation, reflux, bloating, and dysphagia.

Many people with EDS are initially diagnosed with conditions like irritable bowel syndrome (IBS) or GERD, often without an understanding of the underlying connective tissue disorder contributing to these symptoms.

The Hidden Link: EDS and EoE

A landmark 2013 study by Abonia et al. found that patients with inherited connective tissue disorders—including EDS—had an eightfold increased risk of developing EoE compared to the general population. These patients, now considered to have a distinct clinical subtype known as “EoE-CTD,” presented with both connective tissue features (like hypermobility and Marfanoid appearance) and classic EoE symptoms.

Meanwhile, a 2024 study published in The Journal of Pediatric Gastroenterology and Nutrition and reported by the EOS Network found that 21% of pediatric and young adult patients with hEDS or Joint Hypermobility Syndrome (JHS) who had GI symptoms were diagnosed with EoE. Constipation and dysphagia were the most common symptoms, but EoE was the leading histological diagnosis found during endoscopy.

These findings suggest that EoE is not simply a coincidental comorbidity in patients with EDS—it may be directly related to the underlying connective tissue dysfunction and immune dysregulation. The linke between EDS, EOE, and immune dysregulation, was previously highlighted in an article by The EDS Clinic about the link between EoE and MCAS.

Genetic and Molecular Connections

There is increasing interest in the shared genetic and molecular pathways between EDS and EoE, particularly in the TGF-β (transforming growth factor beta) signaling pathway, which regulates immune responses and connective tissue repair.

The same study by Abonia et al. found that patients with EoE-CTD had distinct gene expression patterns, including alterations in genes like COL8A2 and TGFBR1, both of which are associated with connective tissue integrity and inflammation. Some patients with EDS also had mutations in FBN1, the gene implicated in Marfan syndrome, which is known to elevate TGF-β levels. Elevated TGF-β has also been detected in esophageal biopsies from patients with EoE.

This overlap suggests that in some patients, the connective tissue abnormalities of EDS may influence immune responses in the esophagus, predisposing them to EoE.

Clinical Implications: A Call for Integrated Care

Patients with EDS frequently report GI symptoms that are often dismissed as functional or psychosomatic. However, these studies indicate that clinicians should have a low threshold for referring EDS patients with dysphagia or refractory reflux for endoscopy and biopsy to evaluate for EoE or other eosinophilic gastrointestinal diseases.

Likewise, patients with EoE—especially those with joint hypermobility, Marfanoid features, or a history of dislocations—should be evaluated for underlying connective tissue disorders. Recognizing the EoE-CTD overlap can prevent years of misdiagnosis and improve treatment outcomes.

The Patient Perspective

Stories like that of the Schroeder family, as featured in Patient Worthy, illustrate the real-world complexity of these overlapping conditions. Multiple members of the family were diagnosed with combinations of EDS, EoE, and POTS (postural orthostatic tachycardia syndrome). Their journey underscores the need for better awareness and earlier diagnosis—and the importance of family history in complex disorders.

A Path Forward

The EDS and EoE connection is an evolving field with many unanswered questions. What role does the microbiome play? How can immune-modulating therapies like biologics or anti-TGF-β treatments be used to treat this subset of patients? Can early screening improve outcomes?

While more research is needed, what’s already clear is this: EoE and EDS are not separate silos—they are part of a broader picture of connective tissue and immune system interplay. Recognizing their overlap is essential for improving quality of life for thousands of patients.

References

1. Abonia JP, et al. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J Allergy Clin Immunol. 2013.
2. Kottyan LC, Rothenberg ME. Genetics of eosinophilic esophagitis. Mucosal Immunol. 2017.
3. Lee K, et al. Eosinophilic Esophagitis Is an Underlying Cause for Dysphagia in Children. Front Pediatr. 2018.
4. Lucendo AJ, et al. Disease associations in eosinophilic oesophagitis and other eosinophilic gastrointestinal disorders. ScienceDirect. 2015.
5. Schroeder Family. From EoE and POTS to EDS and Intussusception. Patient Worthy. 2023.
6. Mukkada VA, et al. EoE: a prevalent disease at all ages. Clin Gastroenterol Hepatol. 2017.
7. Rothenberg ME, et al. Eosinophilic esophagitis: escalating epidemiology. J Allergy Clin Immunol. 2013.

‍